Process for producing optically active β-hydroxy-α-aminocarboxylic acid derivative

Abstract

There is provided a process for efficiently producing an anti form of an optically active β-hydroxy-α-aminocarboxylic acid derivative that is useful as an intermediate for pharmaceuticals and agrochemicals. The process for producing optically active β-hydroxy-α-aminocarboxylic acid derivative of formula (2) or (3) therein R 1 is substituted or unsubstituted C 1-20 alkyl group, or substituted or unsubstituted C 4-12 aromatic group, R 2 is substituted or unsubstituted C 1-20 alkyl group, or substituted or unsubstituted C 4-12 aromatic group, comprising subjecting an α-aminoacyl acetic acid ester compound of formula (1) wherein R 1 and R 2 have the same meaning as the above, to hydrogenation by catalytic asymmetric hydrogenation in the presence of an acid by using as a catalyst a rhodium complex containing as a ligand an optically active compound of formula (4), (4′) or (5) characterized in that the hydrogenation is conducted in the presence of an acetic acid salt.

1. A process for producing optically active β-hydroxy-α-aminocarboxylic acid compound of formula (2) or (3) 
       
         
           
           
               
               
           
         
         wherein R 1  is either
 C 1-20  alkyl group wherein the C 1-20  alkyl group may be arbitrarily substituted with
 C 4-12  aromatic group that may be arbitrarily substituted with halogen atom, C 1-6  alkyl group, C 1-6  alkoxy group, C 1-6  alkoxycarbonyl group, C 1-6  alkylcarbonyloxy group or CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl group, 
 C 1-6  alkoxy group, 
 C 1-6  alkoxycarbonyl group, or 
 CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl group, 
 
 or R 1  is C 4-12  aromatic group that may be arbitrarily substituted with
 halogen atom, 
 C 1-6  alkyl group, 
 C 1-6  alkoxy group, 
 C 1-6  alkoxycarbonyl group, 
 C 1-6  alkylcarbonyloxy group, or 
 CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl, wherein the C 1-6  alkyl group, C 1-6  alkoxy group, C 1-6  alkoxycarbonyl group and C 1-6  alkylcarbonyloxy group may be arbitrarily substituted with C 4-12  aromatic group that may be arbitrarily substituted with halogen atom, 
 
 
         R 2  is either
 C 1-20  alkyl group wherein the C 1-20  alkyl group may be arbitrarily substituted with
 C 4-12  aromatic group that may be arbitrarily substituted with halogen atom, C 1-6  alkyl group, C 1-6  alkoxy group, C 1-6  alkoxycarbonyl group, C 1-6  alkylcarbonyloxy group or CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl group, 
 C 1-6  alkoxy group, 
 C 1-6  alkoxycarbonyl group, or 
 CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl group, 
 
 or R 2  is C 4-12  aromatic group that may be arbitrarily substituted with halogen atom, C 1-6  alkyl group, C 1-6  alkoxy group, C 1-6  alkoxycarbonyl group, C 1-6  alkylcarbonyloxy group or CONR a R b  wherein R a  and R b  are independently of each other are hydrogen atom or C 1-6  alkyl group, 
 
       
       the process comprising subjecting an α-aminoacyl acetic acid ester compound of formula (1) 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  have the same meaning as the above, to hydrogenation by catalytic asymmetric hydrogenation in the presence of an acid by using as a catalyst a rhodium complex containing as a ligand an optically active compound of formula (4), (4′) or (5) 
       
       
         
           
           
               
               
           
         
         wherein R 3  and R 4  are independently of each other are
 phenyl group that may be arbitrarily substituted with C 1-4  alkyl group or C 1-4  alkoxy group wherein the C 1-4  alkyl group and C 1-4  alkoxy group may be arbitrarily substituted with fluorine atom, 
 C 1-7  alkyl group or 
 2-furyl group, 
 
         R 6  is phenyl group, naphthyl group (the phenyl group and naphthyl group may be arbitrarily substituted with C 1-6  alkyl group or C 1-6  alkoxy group), cyclopentyl group or cyclohexyl group, 
         R 7  is methyl group or methoxy group, 
         R 8  is hydrogen atom, methyl group, methoxy group or chlorine atom, and 
         R 9  is hydrogen atom, methyl group, methoxy group, dimethylamino group or diethylamino group, and absolute configuration is either S or R, 
         wherein the hydrogenation is conducted in the presence of an acetic acid salt. 
       
     
     
       2. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein the ligand of the rhodium complex is the optically active compound of formula (4) or (4′). 
     
     
       3. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 2 , wherein
 R 3  is phenyl group, cyclohexyl group, 2-furyl group, 3,5-bistrifluoromethylphenyl group, 4-trifluoromethylphenyl group or 3,5-dimethyl-4-methoxyphenyl group, and 
 R 4  is tert-butyl group, cyclohexyl group, phenyl group or 3,5-dimethylphenyl group. 
 
     
     
       4. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 3 , wherein the ligand is (R)-(−)-1-[(S)-2-(bis(4-trifluoromethylphenyl)phosphino)ferrocenyl]ethyl-di-tert-butylphosphine, (R)-(−)-1-[(S)-2-(di(3,5-bistrifluoromethylphenyl)phosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (R)-(−)-1-[(S)-2-(di(3,5-bistrifluoromethylphenyl)phosphino)ferrocenyl]ethyl-di(3,5-dimethylphenyl)phosphine, (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine, (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (S)-(+)-1-[(R)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (S)-(+)-1-[(R)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-diphenylphosphine, (R)-(−)-1-[(S)-2-(bis(3,5-dimethyl-4-methoxyphenyl)phosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (S)-(+)-1-[(R)-2-(di-2-furylphosphino)ferrocenyl]ethyl-di(3,5-dimethylphenyl)phosphine, (R)-(−)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine, (S)-(+)-1-[(R)-2(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine, (R)-(−)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (S)-(+)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylphosphine, (R)-(−)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-diphenylphosphine or (R)-(−)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-di(3,5-dimethylphenyl)phosphine. 
     
     
       5. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 4 , wherein the ligand is (R)-(−)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine. 
     
     
       6. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein the ligand of the rhodium complex is the optically active compound of formula (5). 
     
     
       7. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 6 , wherein
 R 6  is cyclohexyl group, phenyl group, 4-methylphenyl group, 4-methoxyphenyl group or 4-tert-butylphenyl group, 
 R 7  is methyl group or methoxy group, 
 R 8  is hydrogen atom or methoxy group, and 
 R 9  is hydrogen atom, methyl group or dimethylamino group. 
 
     
     
       8. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 7 , wherein the ligand is 2,2′-dimethyl-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′-dimethyl-6,6′-bis(dicyclohexylphosphino)-1,1′-biphenyl, 2,2′-dimethyl-4,4′-bis(dimethylamino)-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′,4,4′-tetramethyl-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′-dimethoxy-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′,3,3′-tetramethoxy-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′,4,4′-tetramethyl-3,3′-dimethoxy-6,6′-bis(diphenylphosphino)-1,1′-biphenyl, 2,2′-dimethyl-6,6′-bis(di-4-methylphenylphosphino)-1,1′-biphenyl, 2,2′-dimethyl-6,6′-bis(di-4-tert-butylphenylphosphino)-1,1′-biphenyl or 2,2′,4,4′-tetramethyl-3,3′-dimethoxy-6,6′-bis(di-4-methoxyphenylphosphino)-1,1′-biphenyl. 
     
     
       9. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 8 , wherein the ligand is 2,2′-dimethoxy-6,6′-bis(diphenylphosphino)-1,1′-biphenyl. 
     
     
       10. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein the acid is a strong acid. 
     
     
       11. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein acetic acid is used as a solvent. 
     
     
       12. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein the acetic acid salt is sodium acetate. 
     
     
       13. The process for producing optically active β-hydroxy-α-aminocarboxylic acid compound according to  claim 1 , wherein the rhodium complex is a compound prepared from [RhCl(nbd)] 2  or [Rh(nbd) 2 ]BF 4  wherein nbd is norbornadiene, and the ligand.